Analog Modeling of Human Cognitive Functions with Tripartite Synapses

Searching for an understanding of how the brain supports conscious processes, cognitive scientists have proposed two main classes of theory: Global Workspace and Information Integration theories. These theories seem to be complementary, but both still lack grounding in terms of brain mechanisms responsible for the production of coherent and unitary conscious states. Here we propose following James Robertson's "Astrocentric Hypothesis" - that conscious processing is based on analog computing in astrocytes. The "hardware" for these computations is calcium waves mediated by adenosine triphosphate signaling. Besides presenting our version of this hypothesis, we also review recent findings on astrocyte morphology that lend support to their functioning as Local Hubs (composed of protoplasmic astrocytes) that integrate synaptic activity, and as a Master Hub (composed, in the human brain, by a combination of interlaminar, fibrous, polarized and varicose projection astrocytes) that integrates whole-brain activity.

Astrocytes and human cognition: Modeling information integration and modulation of neuronal activity

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Evaluation of Paracoccidioides brasiliensis exoantigen in the detection of delayed dermal hypersensitivity in experimental and human paracoccidioidomycosis

The exoantigen of Paracoccidioides brasiliensis standardized by Camargo et al. [1] (AgR) was used to evaluate the in vivo and in vitro cell immune response of experimental animals and of patients with paracoccidioidomycosis (PBM). Fava Netto antigen (AgF) was tested in parallel as a control antigen. The study was conducted with mice and guinea pigs infected with P. brasiliensis or immunized with its fungal antigens, on patients with PBM and on their respective control groups. The cell immune response was analysed by skin tests, and by the macrophage and leucocyte migration inhibition tests (MMIT and LMIT) in the animals and in the patients, respectively. The skin test with AgR as paracoccidioidin was positive in infected or immunized mice and guinea pigs and negative in control animals. The skin tests with AgR (24 h) showed 96.7% positivity in patients with PBM and were negative in control individuals. Histopathological study of the in vivo tests in the different experimental models was consistent with a delayed hypersensitivity response (DHR). Immunohistochemical study of the skin tests of PBM patients demonstrated a predominance of T lymphocytes, confirming the nature of a DHR to the fungal antigens. The in vitro cell immune response showed variable results for the various experimental models, i.e. significant rates of MMIT in immunized mice, a tendency to positivity in infected guinea pigs, and the absence of migration inhibition in PBM patients. Taken together, the data indicate that the AgR is efficient as paracoccidioidin in the evaluation of DHR in PBM, with an optimum time of reading the test of 24 h.

Intrapulpar temperature during continuous CO2 laser irradiation in human molars: An in vitro study

To establish safety parameters, we in vitro studied the increase in intrapulpal temperature caused by the use of a cw CO2 laser. A thermistor was implanted in the inner part of the pulpal chamber of 25 human lower third molars to measure the intrapulpal temperature produced by laser powers between 2-10 W and exposure times of 0.5-25.0 s. The Pearson linear correlation factor applied to the measured values showed there is a direct relationship between the independent variable and the applied power. A variance analysis produced the linear regression equation: T=1.10+(0.127)E where T is the temperature and E the energy. The results showed that, with a power of 4 W and maximum exposure time of 2.5 s (10 J) and a power density of 12738.85 W cm-2, there will be no damaging reactions affecting the pulpal tissues.

Intrauterine dentistry: an integrated model of prevention.

Intrauterine Dentistry is a highly relevant subject of our time. The use of preventive measures in the intrauterine stage can avoid several diseases, among these, dental caries. The WHO advises that from the 4th month of pregnancy, women should avoid the intake of sugar, so that the fetus, future child, does not develop an exaggerated attraction for these types of foods, thus being susceptible to caries. Through questionnaires sent to gynecologist-obstetricians and dentists, this research investigated the information they have about this subject and how they instruct their patients. Questionnaires were also sent to pregnant women requesting information about the instructions they had received for the prevention of oral diseases of their fetus. Seventy-one percent of the dentists and 80% of the gynecologist-obstetricians reported having instructed the pregnant women to reduce the intake of sugar. However, only 13.6% of the dentists and no gynecologist-obstetrician instructed the reduction of sugar intake between the 12th and 18th week of pregnancy. A total of 42.2% of the pregnant women referred to these instructions, but none received instruction as to the specific period of the 12th and 18th week. An ideal model of treatment for pregnant women must include integrated and multiprofessional treatment, in which general dentists and gynecologist-obstetricians work together with the participation of the patient.

Poisoning of mice by Baccharis coridifolia: An experimental model

The poisonous plant Baccharis coridifotia causes necrosis in lymphoid tissues and the gastrointestinal tract of cattle, horses, sheep and rabbits. An experimental poisoning of mice was undertaken to establish an experimental model in a laboratory animal specie. A single 5 to 8-g/kg dose of a suspension of the plant was administered by gavage to II mice. To 3 other control mice, the same volume of water was administered. Plant-dosed mice manifested clinical effects after 12 h: tachipnea, trembles, dehydration and prostration. Most of the dosed mice died 14 to 33 h after plant administration-3 survived for 12 d. Six mice had remarkable necrosis of the germinative center of secondary follicles in lymph nodes and spleen; 3 mice had necrosis of lymphoid tissues in intestine and thymus. Mice reproduce most of the lesions observed in naturally poisoned cattle and the use of this specie as an experimental model is valid.

Chloroquine inhibits Paracoccidioides brasiliensis survival within human monocytes by limiting the availability of intracellular iron

The mechanisms used by Paracoccidioides brasiliensis (Pb 18) to survive into monocytes are not clear. Cellular iron metabolism is of critical importance to the growth of several intracellular pathogens, including P. brasiliensis, whose capacity to multiply in mononuclear phagocytes is dependent on the availability of intracellular iron. Chloroquine, by virtue of its basic properties, has been shown to prevent release of iron from holotransferrin by raising endocytic and lysosomal pH, and thereby interfering with normal iron metabolism. Then, in view of this, we have studied the effects of CHLOR on P. brasiliensis multiplication in human monocytes and its effect on the murine paracoccidioidomycosis. CHLOR induced human monocytes to kill P. brasiliensis. The effect of CHLOR was reversed by FeNTA, an iron compound that is soluble at neutral to alkaline pH, but not by holotransferrin, which releases iron only in an acidic environment. CHLOR treatment of Pb 18-infected BALB/c mice significantly reduced the viable fungi recovery from lungs, during three different periods of evaluation, in a dose-dependent manner. This study demonstrates that iron is of critical importance to the survival of P. brasiliensis yeasts within human monocytes and the CHLOR treatment in vitro induces Pb 18 yeast-killing by monocytes by restricting the availability of intracellular iron. Besides, the CHLOR treatment in vivo significantly reduces the number of organisms in the lungs of Pb-infected mice protecting them from several infections. Thus, CHLOR was effective in the treatment of murine paracoccidioidomycosis, suggesting the potential use of this drug in patients' treatment.

The inhibition of 5-enolpyruvylshikimate-3-phosphate synthase as a model for development of novel antimicrobials

EPSP synthase (EPSPS) is an essential enzyme in the shikimate pathway, transferring the enolpyruvyl group of phosphoenolpyruvate to shikimate-3-phosphate to form 5-enolpyruvyl-3-shikimate phosphate and inorganic phosphate. This enzyme is composed of two domains, which are formed by three copies of βαβαββ-folding units; in between there are two crossover chain segments hinging the nearly topologically symmetrical domains together and allowing conformational changes necessary for substrate conversion. The reaction is ordered with shikimate-3-phosphate binding first, followed by phosphoenolpyruvate, and then by the subsequent release of phosphate and EPSP. N-[phosphomethyl]glycine (glyphosate) is the commercial inhibitor of this enzyme. Apparently, the binding of shikimate-3-phosphate is necessary for glyphosate binding, since it induces the closure of the two domains to form the active site in the interdomain cleft. However, it is somehow controversial whether binding of shikimate-3-phosphate alone is enough to induce the complete conversion to the closed state. The phosphoenolpyruvate binding site seems to be located mainly on the C-terminal domain, while the binding site of shikimate-3-phosphate is located primarily in the N-terminal domain residues. However, recent results demonstrate that the active site of the enzyme undergoes structural changes upon inhibitor binding on a scale that cannot be predicted by conventional computational methods. Studies of molecular docking based on the interaction of known EPSPS structures with (R)- phosphonate TI analogue reveal that more experimental data on the structure and dynamics of various EPSPS-ligand complexes are needed to more effectively apply structure-based drug design of this enzyme in the future. © 2007 Bentham Science Publishers Ltd.

The use of planarians as in vivo animal model to study laser biomodulation effects

A variety of effects is attributed to the photo stimulation of tissues, such as improved healing of ulcers, analgesic and anti-inflammatory effects, stimulation of the proliferation of cells of different origins and stimulation of bone repair. Some investigations that make qualitative evaluations, like wound healing and evaluation of pain and edema, can be conducted in human subjects. However, deeper investigations on the mechanisms of action of the light stimulus and other quantitative works that requires biopsies or destructive analysis has to be carried out in animal models or in cell cultures. In this work, we propose the use of planarians as a model to study laser-tissue interaction. Contrasting with cell cultures and unicellular organisms, planarians are among the simplest organism having tissue layers, central nerve system, digestive and excretory system that might have been platforms for the evolution of the complex and highly organized tissues and organs found in higher organisms. For the present study, 685 nm laser radiation was employed. Planarians were cut transversally, in a plane posterior to the auricles. The body fragments were left to regenerate and the proliferation dynamics of stem cells was studied by using histological analysis. Maximum cell count was obtained for the laser treated group at the 4th experimental day. At that experimental time, we also had the largest difference between the irradiated and the non-irradiated control group. We concluded that the studied flatworm could be an interesting animal model for in vivo studies of laser-tissue interactions.

Botucatu, Brazil: A Regional Community Palliative Care Model

The Pain Management and Palliative Care Service in the Department of Anesthesia at Botucatu Medical School, UNESP is a pioneer in Brazil. Based on an interdisciplinary team that provides specialized inpatient, ambulatory outpatient, and home care to patients in Botucatu and the surrounding region, the service is also able to provide extensive educational opportunities in pain management and palliative care for medical students, anesthesia residents, practicing anesthetists, and nurses. © 2007 U.S. Cancer Pain Relief Committee.

Comparative analysis of human and bovine teeth: Radiographic density

Since bovine teeth have been used as substitutes for human teeth in in vitro dental studies, the aim of this study was to compare the radiographic density of bovine teeth with that of human teeth to evaluate their usability for radiographic studies. Thirty bovine and twenty human teeth were cut transversally in 1 millimeter-thick slices. The slices were X-rayed using a digital radiographic system and an intraoral X-ray machine at 65 kVp and 7 mA. The exposure time (0.08 s) and the target-sensor distance (40 cm) were standardized for all the radiographs. The radiographic densities of the enamel, coronal dentin and radicular dentin of each slice were obtained separately using the histogram tool of Adobe Photoshop 7.0 software. The mean radiographic densities of the enamel, coronal dentin and radicular dentin were calculated by the arithmetic mean of the slices of each tooth. One-way ANOVA demonstrated statistically significant differences for the densities of bovine and human enamel (p < 0.05) and for bovine and human coronal dentin (p < 0.05). No statistically significant differences were found for the bovine and human radicular dentin (p > 0.05). Based on the results, the authors concluded that: a) the radiographic density of bovine enamel is significantly higher than that of human enamel; b) the radiodensity of bovine coronal dentin is statistically lower than the radiodensity of human coronal dentin; bovine radicular dentin is also less radiodense than human radicular dentin, although this difference was not statistically significant; c) bovine teeth should be used with care in radiographic in vitro studies.

Comparison of resin push-out strength to root dentin of bovine- and human-teeth

Aim : To compare the push-out strength of bovine- and human-root dentin and, thus, evaluate the suitability of bovine-root dentin to substitute human-root dentin for bond strength testing. Materials and Methods : Ten single-rooted human-teeth and ten bovine incisors were prepared using a #3 bur of a fiber post system (12 mm long). The posts were duplicated with resin cement (Duolink). The root canals were treated with All Bond 2 adhesive system and the resin posts were cemented using Duolink. The specimens were cut perpendicular to their long axis, yielding disc-specimens with 1.5 mm thickness, which were submitted to a push-out test (1 mm/min). Ten bond strength values per group (n = 10) were used for statistical analysis (Student t test, a =.05). Results : Statistically significant differences were found for the bond strength values between bovine- (4.1 1.3 MPa) and human-root dentin (8.6 5.7 MPa) (P =.0001). Conclusion : The push-out strengths of bovine- and human-root dentin were statistically different.

Human capital formation and the linkage between trade and poverty: the cases of Costa Rica and Nicaragua

Includes bibliography

FTMOntology: An ontology to fill the semantic gap between music, mood, personality, and human physiology

This paper presents a domain ontology, the FeelingTheMusic Ontology - FTMOntology. FTMOntology is designed to represent the complex domain of music and how it relates to other domains like mood, personality and physiology. This includes representing the main concepts and relations of music domain with each of the above-mentioned domains. The concepts and relations between music, mood, personality and physiology. The main contribution of this work is to model and relate these different domains in a consistent ontology. © 2011 Springer-Verlag.

A malware detection system inspired on the human immune system

Malicious programs (malware) can cause severe damage on computer systems and data. The mechanism that the human immune system uses to detect and protect from organisms that threaten the human body is efficient and can be adapted to detect malware attacks. In this paper we propose a system to perform malware distributed collection, analysis and detection, this last inspired by the human immune system. After collecting malware samples from Internet, they are dynamically analyzed so as to provide execution traces at the operating system level and network flows that are used to create a behavioral model and to generate a detection signature. Those signatures serve as input to a malware detector, acting as the antibodies in the antigen detection process. This allows us to understand the malware attack and aids in the infection removal procedures. © 2012 Springer-Verlag.